Immunotherapy as an Antifungal Strategy in Immune Compromised Hosts
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MYCOLOGY (M NOVERR, SECTION EDITOR)
Immunotherapy as an Antifungal Strategy in Immune Compromised Hosts Wilfried Posch 1
&
Doris Wilflingseder 1 & Cornelia Lass-Flörl 1
# The Author(s) 2020
Abstract Purpose of Review IFIs cause high morbidity and mortality in the immunocompromised host worldwide. Although highly effective, conventional antifungal chemotherapy faces new challenges due to late diagnosis and increasing numbers of drugresistant fungal strains. Thus, antifungal immunotherapy represents a viable treatment option, and recent advances in the field are summarized in this review. Recent Findings Antifungal immunotherapies include application of immune cells as well as the administration of cytokines, growth factors, and antibodies. Novel strategies to treat IFIs in the immunocompromised host target intracellular signaling pathways using SMTs such as checkpoint inhibitors. Summary Studies using cytokines or chemokines exerted a potential adjuvant role to conventional antifungal therapy, but issues on toxicity for some agents have to be resolved. Cell-based immunotherapies are very labor-intense and costly, but NK cell transfer and CAR T cell therapy provide exciting strategies to combat IFIs. Antibody-mediated protection and checkpoint inhibition are additional novel immunotherapeutic approaches. Keywords Invasive fungal infections . Immunotherapy . Innate and adaptive immunity . Cell therapy . Cytokine therapy . Checkpoint inhibitors
Introduction Opportunistic fungal infections are still a major health problem in immunocompromised patients worldwide and cause an estimated 1.6 million deaths each year [1]. This reported high morbidity and mortality of fungal infections result from the lack of reliable and fast diagnostics as well as from the limited options of antifungals especially for the treatment of resistant fungi [2]. Patients with prolonged neutropenia, allogeneic hematopoietic stem cell transplant (HSCT), solid organ transplant (SOT), inherited or acquired immunodeficiencies, i.e., AIDS, or corticosteroid use are at highest risk of lifethreatening invasive fungal infections (IFIs) [3]. Although abundance of, e.g., Aspergillus conidia is high and hundreds This article is part of the Topical Collection on Mycology * Wilfried Posch [email protected] 1
Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Schöpfstrasse 41, 6020 Innsbruck, Austria
are inhaled every day by each person, immunocompetent individuals are protected due to mucociliary clearance and the presence of phagocytic cells in the lungs [4, 5]. Thus, IFIs are almost exclusively observed in immunocompromised hosts. In most cases, IFIs are caused by fungi from the genera Candida, Aspergillus, Cryptococcus, or Pneumocystis, but until today, these infections are treated with antifungal drugs, since no vaccine is currently available [4]. At the moment, there are three classes of antifungal drugs available and in clinical use: azoles (e.g., fluconazole), polyenes (e.g., amphotericin B, AmB), and echinoc
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